CN105017232A - Synthesis method of triazole bactericide - Google Patents
Synthesis method of triazole bactericide Download PDFInfo
- Publication number
- CN105017232A CN105017232A CN201510455074.9A CN201510455074A CN105017232A CN 105017232 A CN105017232 A CN 105017232A CN 201510455074 A CN201510455074 A CN 201510455074A CN 105017232 A CN105017232 A CN 105017232A
- Authority
- CN
- China
- Prior art keywords
- triazole
- bactericidal agent
- reaction
- triazole bactericidal
- synthetic method
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/06—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
Abstract
The invention relates to a synthesis method of a triazole bactericide, which comprises the following steps: carrying out condensation reaction on 4-amino-1,2,4-triazole in the presence of an organic solvent to obtain an organic salt, carrying out deamination reaction on the organic salt in the presence of dilute hydrochloric acid and a sodium nitrate water solution, and after the reaction finishes, carrying out after-treatment to obtain the triazole bactericide. The method avoids generation of the byproduct 1,3,4-triazole, and uses the 4-amino-1,2,4-triazole instead of 4-H-1,2,4-triazole to react with the halogenated compound; the deamination reaction is performed to obtain the single 1,2,4-triazole substitute; and the compound is further purified to satisfy the market demand. Compared with the prior art, the method has the advantages of high yield, low cost, fewer three wastes and the like.
Description
Technical field
The present invention relates to a kind of synthetic method of triazole bactericidal agent.
Background technology
1, 2, 4-triazole substituent is widely used in medicine and pesticide field, normally by 1, 2, 4-triazole and alkylating reagent carry out alkylated reaction and obtain 1, 2, 4-triazole substituent, primary synthetic methods as depicted in figs. 1 and 2, these two kinds of synthetic methods all utilize alkylating reagent and 4-H-1, 2, 4-triazole at alkali as under catalyst action, there is alkylated reaction, obtain 1, 2, 4-triazole substituent, also obtain by product 1 simultaneously, 3, 4-triazole substituent, by-products content is about 10 ~ 15%, due to the existence of the by product of this ratio, alkylation yield is about 80%, prior art is difficult to improve its reaction yield, by product 1 simultaneously, 3, 4-triazole substituent can only process as " three wastes ", all certain influence is caused to environment and cost.Further, due to the content about 10 ~ 18% of 1,3,4-triazole substituent, this can bring great difficulty to the purifying of product, from 1, separates 1 in 2,4 triazole substituents, the technology of 3,4-triazole substituent becomes the core in production process, also reduces costs, the creation of value basic.
Summary of the invention
Technical problem to be solved by this invention is to provide the synthetic method of the triazole bactericidal agent that one can avoid 1,3,4-triazole substituent to produce.
In order to solve the problems of the technologies described above, the present invention adopts following technical scheme:
A kind of synthetic method of triazole bactericidal agent, by 4-amino-1,2,4-triazole and halogenated compound are in presence of organic solvent, carry out condensation reaction and obtain organic salt, by described organic salt under the existence of dilute hydrochloric acid and sodium nitrite in aqueous solution, carry out the reaction that deaminizes, described triazole bactericidal agent is obtained through aftertreatment after reaction terminates
Wherein, the structural formula of described halogenated compound is:
The structural formula of described organic salt is:
The structural formula of described triazole bactericidal agent is:
Wherein, R
1for alkyl, aryl or halogenated aryl hydrocarbon base, halo replaces for part or entirely replaces; R
2for alkyl; X is Cl or Br.
Preferably, the temperature of carrying out described condensation reaction is 0 ~ 200 DEG C.
Further preferably, the temperature of carrying out described condensation reaction is 50 ~ 150 DEG C.
More preferably, the temperature of carrying out described condensation reaction is 80 ~ 100 DEG C.
The most preferably, the temperature of carrying out described condensation reaction is 85 ~ 95 DEG C.
Preferably, described organic solvent is for being selected from methyl alcohol, ethanol, propyl carbinol, Virahol, N, one or more mixed solvent in dinethylformamide (DMF), N,N-dimethylacetamide (DMA), N-Methyl pyrrolidone (NMP), diethylene glycol dimethyl ether, toluene.
Preferably, the temperature of carrying out the described reaction that deaminizes is 0 ~ 150 DEG C.
Further preferably, the temperature of carrying out the described reaction that deaminizes is 10 ~ 80 DEG C.
More preferably, the temperature of carrying out the described reaction that deaminizes is 10 ~ 40 DEG C.
Preferably, the molar ratio of amino-1,2, the 4-triazole of described 4-and described halogenated compound is 1.0 ~ 2.0:1.0.
Further preferably, the molar ratio of amino-1,2, the 4-triazole of described 4-and described halogenated compound is 1.1 ~ 1.5:1.0.
Preferably, the mass percent concentration of described dilute hydrochloric acid is 1% ~ 30%.
Further preferably, the mass percent concentration of described dilute hydrochloric acid is 10% ~ 20%.
Preferably, the mass percent concentration of described sodium nitrite in aqueous solution is 10% ~ 50%.
Further preferably, the mass percent concentration of described sodium nitrite in aqueous solution is 20% ~ 30%.
Preferably, described R
1for
or
described R
2for methyl or propyl group.
Further preferably, described halogenated compound is
or
When described halogenated compound is
time, the described triazole bactericidal agent that reaction generates is Wocosin 50TK.
When described halogenated compound is
time, the described triazole bactericidal agent that reaction generates is difenoconazole.
Preferably, the concrete reactions steps of described triazole bactericidal agent is:
Step (1) condensation reaction: by described 4-amino-1,2,4-triazole and described halogenated compound are dissolved in described organic solvent, carry out condensation reaction 7 ~ 10 hours at 0 ~ 200 DEG C, reaction terminate after, after filtration, washing obtain described organic salt;
Step (2) deaminizes reaction: be dissolved in by described organic salt in described dilute hydrochloric acid, be cooled to 0 DEG C ~ 10 DEG C, sodium nitrite in aqueous solution described in dropping, after dropping terminates, insulation reaction 1 ~ 3h at 0 ~ 150 DEG C, after reaction terminates, the pH regulating reaction system is 6.5 ~ 7.5, then, at 70 ~ 90 DEG C, obtain oily matter through layering, washing, then obtain described triazole bactericidal agent to after the decolouring of described oily matter, crystallization, filtration, drying.
Owing to adopting above technical scheme, the present invention compared with prior art tool has the following advantages:
Present invention, avoiding the generation of by product 1,3,4-triazole substituent, 4-H-1 is replaced with amino-1,2, the 4-triazole of 4-, 2,4-triazole and halogenated compound reaction, by the reaction that deaminizes, obtain single 1,2,4-triazole substituent, more further purifying is carried out to compound, to meet the need of market.The present invention compared with prior art, has the advantages such as yield is high, cost is low, and " three wastes " are few.
Accompanying drawing explanation
Accompanying drawing 1 is a kind of synthetic route chart of 1,2,4-triazole substituent in prior art;
Accompanying drawing 2 be in prior art 1,2,4-triazole substituent another in synthetic route chart;
Accompanying drawing 3 is synthetic route chart of the present invention;
Accompanying drawing 4 is the synthetic route chart of embodiment 1;
Accompanying drawing 5 is the synthetic route chart of embodiment 2.
Embodiment
Below in conjunction with specific embodiment, technical scheme of the present invention is further described, but the present invention should not be limited to these embodiments.
Embodiment 1
Synthetic route is see Fig. 4.
Condensation reaction: by bromine ketal (compound 1,37.3g, 95%, 0.1mol) and 4-amino-1,2,4-triazole (compound 2,9.4g, 98%, 0.11mol) be dissolved in propyl carbinol (100g), be warming up to 100 DEG C, be incubated 8 hours, insulation terminates, sampling analysis, bromine ketal (compound 1) content≤10%, be cooled to room temperature, filter, rinsing, obtain solid chemical compound 3 (40g, wet product), mother liquor can be applied mechanically to next batch.
Deaminize reaction: be dissolved in by compound 3 (40g, wet product) in dilute hydrochloric acid (120g, 10%), be cooled to 10 DEG C, drip sodium nitrite in aqueous solution (30g, 30%, 0.13mol), drip off, be naturally warming up to room temperature, be incubated 2 hours, regulate PH to neutral with liquid caustic soda, be warming up to 80 DEG C, layering, then wash twice, obtain oily matter, again product Wocosin 50TK (29g, content 95.8%) is obtained, yield 81.2% to oily matter decolouring, decolouring.
Embodiment 2
Synthetic route is see Fig. 5.
Condensation reaction: by brominated eopxy (compound 4,44g, 95%, 0.1mol) and 4-amino-1,2,4-triazole (compound 2,10.3g, 98%, 0.12mol) be dissolved in diethylene glycol dimethyl ether (100g), be warming up to 80 DEG C, be incubated 8 hours, insulation terminates, sampling analysis, brominated eopxy (compound 4) content≤10%, be cooled to room temperature, filter, rinsing, obtain solid chemical compound 5 (50g, wet product), mother liquor can be applied mechanically to next batch.
Deaminize reaction: by compound 5 (50g, wet product) be dissolved in dilute hydrochloric acid (120g, 10%) in, be cooled to 5 DEG C, drip sodium nitrite in aqueous solution (42g, 25%, 0.15mol), drip off, be naturally warming up to room temperature, be incubated 2 hours, regulate PH to neutral with liquid caustic soda, be warming up to 80 DEG C, layering, then wash twice, obtain oily matter, again white solid difenoconazole (34.3g, content 96.5%) is obtained, yield 80.8% to oily matter decolouring, crystallization, filtration (mother liquid recycle is to next batch crystallization) drying.
Embodiment 3
Synthetic route is see Fig. 4.
Condensation reaction: by bromine ketal (compound 1,37.3g, 95%, 0.1mol) and 4-amino-1,2,4-triazole (compound 2,11.1g, 98%, 0.13mol) be dissolved in propyl carbinol (100g applies mechanically), be warming up to 90 DEG C, be incubated 8 hours, insulation terminates, sampling analysis, bromine ketal (compound 1) content≤10%, be cooled to room temperature, filter, rinsing, obtain solid chemical compound 3 (41g, wet product), mother liquor can be applied mechanically to next batch.
Deaminize reaction: be dissolved in by compound 3 (41g, wet product) in dilute hydrochloric acid (120g, 20%), be cooled to 10 DEG C, drip sodium nitrite in aqueous solution (30g, 25%, 0.11mol), drip off, be naturally warming up to room temperature, be incubated 2 hours, regulate PH to neutral with liquid caustic soda, be warming up to 40 DEG C, layering, then wash twice, obtain oily matter, again product Wocosin 50TK (33.6g, content 95.8%) is obtained, yield 94.3% to oily matter decolouring, decolouring.
Embodiment 4
Synthetic route is see Fig. 5.
Condensation reaction: by brominated eopxy (compound 4,44g, 95%, 0.1mol) with 4-amino-1,2,4-triazole (compound 2,12.9g, 98%, 0.15mol) be dissolved in diethylene glycol dimethyl ether (100g applies mechanically), be warming up to 90 DEG C, be incubated 8 hours, insulation terminates, sampling analysis, brominated eopxy (compound 4) content≤10%, be cooled to room temperature, filter, rinsing, obtains solid chemical compound 5 (51g, wet product), mother liquor can be applied mechanically to next batch.
Deaminize reaction: by compound 5 (51g, wet product) be dissolved in dilute hydrochloric acid (120g, 20%) in, be cooled to 5 DEG C, drip sodium nitrite in aqueous solution (42g, 25%, 0.15mol), drip off, be naturally warming up to room temperature, be incubated 2 hours, regulate PH to neutral with liquid caustic soda, be warming up to 40 DEG C, layering, then wash twice, obtain oily matter, again white solid difenoconazole (39g, content 97.3%) is obtained, yield 95.0% to oily matter decolouring, crystallization, filtration (mother liquid recycle is to next batch crystallization) drying.
Above-described embodiment is just for illustrating technical conceive of the present invention and feature; its object is to person skilled in the art can be understood content of the present invention and implement according to this; can not limit the scope of the invention with this; all equivalences done according to spirit of the present invention change or modify, and all should be encompassed within protection scope of the present invention.
Claims (10)
1. the synthetic method of a triazole bactericidal agent, it is characterized in that: by 4-amino-1,2,4-triazole and halogenated compound are in presence of organic solvent, carry out condensation reaction and obtain organic salt, by described organic salt under the existence of dilute hydrochloric acid and sodium nitrite in aqueous solution, carry out the reaction that deaminizes, described triazole bactericidal agent is obtained through aftertreatment after reaction terminates
Wherein, the structural formula of described halogenated compound is:
The structural formula of described organic salt is:
The structural formula of described triazole bactericidal agent is:
Wherein, R
1for alkyl, aryl or halogenated aryl hydrocarbon base, halo replaces for part or entirely replaces; R
2for alkyl; X is Cl or Br.
2. the synthetic method of triazole bactericidal agent according to claim 1, is characterized in that: the temperature of carrying out described condensation reaction is 0 ~ 200 DEG C.
3. the synthetic method of triazole bactericidal agent according to claim 1, it is characterized in that: described organic solvent is for being selected from methyl alcohol, ethanol, propyl carbinol, Virahol, N, one or more mixed solvent in dinethylformamide, N,N-dimethylacetamide, N-Methyl pyrrolidone, diethylene glycol dimethyl ether, toluene.
4. the synthetic method of triazole bactericidal agent according to claim 1, is characterized in that: the temperature of carrying out the described reaction that deaminizes is 0 ~ 150 DEG C.
5. the synthetic method of triazole bactericidal agent according to claim 1, is characterized in that: the molar ratio of amino-1,2, the 4-triazole of described 4-and described halogenated compound is 1.0 ~ 2.0:1.0.
6. the synthetic method of triazole bactericidal agent according to claim 1, is characterized in that: the mass percent concentration of described dilute hydrochloric acid is 1% ~ 30%.
7. the synthetic method of triazole bactericidal agent according to claim 1, is characterized in that: the mass percent concentration of described sodium nitrite in aqueous solution is 10% ~ 50%.
8. the synthetic method of triazole bactericidal agent according to claim 1, is characterized in that: described R
1for
described R
2for methyl or propyl group.
9. the synthetic method of triazole bactericidal agent according to claim 8, is characterized in that: described halogenated compound is
10. the synthetic method of triazole bactericidal agent according to claim 1, is characterized in that: the concrete reactions steps of described triazole bactericidal agent is:
Step (1) condensation reaction: by described 4-amino-1,2,4-triazole and described halogenated compound are dissolved in described organic solvent, carry out condensation reaction 7 ~ 10 hours at 0 ~ 200 DEG C, reaction terminate after, after filtration, washing obtain described organic salt;
Step (2) deaminizes reaction: be dissolved in by described organic salt in described dilute hydrochloric acid, be cooled to 0 DEG C ~ 10 DEG C, sodium nitrite in aqueous solution described in dropping, after dropping terminates, insulation reaction 1 ~ 3h at 0 ~ 150 DEG C, after reaction terminates, the pH regulating reaction system is 6.5 ~ 7.5, then, at 70 ~ 90 DEG C, obtain oily matter through layering, washing, then obtain described triazole bactericidal agent to after the decolouring of described oily matter, crystallization, filtration, drying.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201510455074.9A CN105017232B (en) | 2015-07-29 | 2015-07-29 | A kind of synthetic method of triazole bactericidal agent |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201510455074.9A CN105017232B (en) | 2015-07-29 | 2015-07-29 | A kind of synthetic method of triazole bactericidal agent |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN105017232A true CN105017232A (en) | 2015-11-04 |
| CN105017232B CN105017232B (en) | 2018-06-08 |
Family
ID=54407581
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201510455074.9A Active CN105017232B (en) | 2015-07-29 | 2015-07-29 | A kind of synthetic method of triazole bactericidal agent |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN105017232B (en) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106243087A (en) * | 2016-09-12 | 2016-12-21 | 三峡大学 | A kind of triazole ketopyrrolidine series bactericidal agent, synthetic method and application thereof |
| CN113336715B (en) * | 2021-08-04 | 2021-11-23 | 山东海利尔化工有限公司 | Preparation method of triazole compound containing dioxolane and intermediate thereof |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4607045A (en) * | 1984-01-19 | 1986-08-19 | Basf Aktiengesellschaft | Azolylmethylcycloacetals, their preparation and their use as drugs |
| CN103228650A (en) * | 2010-09-30 | 2013-07-31 | 巴斯夫欧洲公司 | A process for the synthesis of thio-riazolo-group containing compounds |
| CN104402871A (en) * | 2014-12-01 | 2015-03-11 | 江苏耕耘化学有限公司 | Method for specifically preparing derivative of 2-(1H-1, 2, 4-triazole-1-methyl)-1, 3-dioxolane |
-
2015
- 2015-07-29 CN CN201510455074.9A patent/CN105017232B/en active Active
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4607045A (en) * | 1984-01-19 | 1986-08-19 | Basf Aktiengesellschaft | Azolylmethylcycloacetals, their preparation and their use as drugs |
| CN103228650A (en) * | 2010-09-30 | 2013-07-31 | 巴斯夫欧洲公司 | A process for the synthesis of thio-riazolo-group containing compounds |
| CN104402871A (en) * | 2014-12-01 | 2015-03-11 | 江苏耕耘化学有限公司 | Method for specifically preparing derivative of 2-(1H-1, 2, 4-triazole-1-methyl)-1, 3-dioxolane |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106243087A (en) * | 2016-09-12 | 2016-12-21 | 三峡大学 | A kind of triazole ketopyrrolidine series bactericidal agent, synthetic method and application thereof |
| CN106243087B (en) * | 2016-09-12 | 2018-10-09 | 三峡大学 | A kind of triazole pyrrolidones series bactericidal agent, synthetic method and its application |
| CN113336715B (en) * | 2021-08-04 | 2021-11-23 | 山东海利尔化工有限公司 | Preparation method of triazole compound containing dioxolane and intermediate thereof |
Also Published As
| Publication number | Publication date |
|---|---|
| CN105017232B (en) | 2018-06-08 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| EP2998299B1 (en) | Preparation method of azoxystrobin | |
| CN101565406B (en) | Preparation process for cyproconazole | |
| JP6719527B2 (en) | Method for preparing azoxystrobin intermediate | |
| CN103965125A (en) | Synthetic method of 3,3'-binitro-5,5'-di-1,2,4-triazole | |
| CN102964313A (en) | Synthetic method of febuxostat | |
| CN102690225B (en) | New synthetic method of bazedoxifene | |
| JP2015500325A5 (en) | ||
| CN104045602A (en) | Improved method for preparing tetrazole for valsartan | |
| CN102516139A (en) | Synthesis method of phenyl sulfide compound | |
| CN105061405A (en) | Preparation method of fimasartan potassium salt hydrate | |
| CN105017232A (en) | Synthesis method of triazole bactericide | |
| CN102875463A (en) | Synthesis method for high-quality and low-cost bispyrithione | |
| CN103193611A (en) | Method for synthesizing m-trifluoromethyl acetophenone | |
| CN102875435A (en) | Organic thiosulfuric acid derivative preparation method | |
| CN104230821A (en) | Method for synthesizing azoxystrobin | |
| CN109796368B (en) | Synthesis method of N' - [ (2S,3S) -2- (benzyloxy) pentan-3-yl ] formylhydrazine | |
| CN104045596B (en) | Method for preparing etoricoxib intermediate 1-(6-methylpyridyl-3-yl)-2-[4-(mesyl)-phenyl]-ethyl-one | |
| CN102757390B (en) | Method for preparing 2-methoxy-4-diazanyl-5-fluoropyrimidine | |
| CN108530380B (en) | Synthesis method of N-methyl-1, 2-benzisothiazolin-3-one | |
| CN109956884A (en) | A kind of preparation method of Phenylmethoxyamine hydrochloride | |
| CN108976122A (en) | The method for preparing 1,3- dicarbonyl compound based on metal hydride/palladium compound system | |
| CN103709039A (en) | Method for synthesizing methyl (ethyl) gallate through catalysis of Cu-mordenite | |
| CN105016984A (en) | Industrial preparation method of 2-(2-ethoxyphenoxy)bromic ether | |
| CN104262332A (en) | Preparation method of olmesartan medoxomil | |
| CN108046999B (en) | Method for preparing antioxidant 1790 intermediate by solvent-free method |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant |